Histidine residues regulate the transition of photoexcited rhodopsin to its active conformation, metarhodopsin II

Charles J. Weitz, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

The biologically active photoproduct of rhodopsin, metarhodopsin II (M II), exists in a pH-sensitive equilibrium with its precursor, metarhodopsin I (M I). Increasing acidity favors M 11, with the midpoint of the pH titration curve at pH 6.4. To test the long-standing proposal that histidine protonation regulates this conformational transition, we characterized mutant rhodopsins in which each of the 6 histidines was replaced by phenylalanine or cysteine. Only mutants substituted at the 3 conserved histidines showed abnormal M I-M II equilibria. Those in which His-211 was replaced by phenylalanine or cysteine formed little or no M 11 at either extreme of pH, whereas mutants substituted at His-65 or at His-152 showed enhanced sensitivity to protons. The simplest interpretation of these results is that His-211 is the site where protonation strongly stabilizes the M I I conformation and that His-65 and His-152 are sites where protonation modestly destabilizes the M 11 conformation.

Original languageEnglish (US)
Pages (from-to)465-472
Number of pages8
JournalNeuron
Volume8
Issue number3
DOIs
StatePublished - 1992

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Rhodopsin
Histidine
Phenylalanine
Cysteine
Protons
metarhodopsins

ASJC Scopus subject areas

  • Neuroscience(all)

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Histidine residues regulate the transition of photoexcited rhodopsin to its active conformation, metarhodopsin II. / Weitz, Charles J.; Nathans, Jeremy.

In: Neuron, Vol. 8, No. 3, 1992, p. 465-472.

Research output: Contribution to journalArticle

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